A double-blind, randomized, multicenter protocol comparing Trimetrexate (TMTX) with leucovorin rescues versus Trimethoprim/sulfamethoxazole in the treatment of moderately severe PCP in AIDS patients. TMTX is very active against P. carinii, and high dose leucovorin protects mammalian cells from TMTX. In initial patients studies TMTX/leucovorin was efficacious with little toxicity.